Role of Induced Sputum and Fractional Exhaled Nitric Oxide Test for Assessing Inflammation in Patients with Bronchiectasis

doi:10.12114/j.issn.1007-9572.2020.00.587

Abstract

Abstract: Background　Bronchiectasis is a common chronic airway inflammatory disease，but varies significantly across individuals.Induced sputum and fractional exhaled nitric oxide（FeNO）have been widely used in the assessment of asthma and chronic obstructive pulmonary disease，but little is known about whether they could be used for evaluating airway inflammation in bronchiectasis.Objective　To evaluate the associations of induced sputum and FeNO with the clinical characteristics and lung function parameters in patients with bronchiectasis，to explore the value of noninvasive airway inflammation tests in stable bronchiectasis.Methods　We enrolled 62 patients with stable bronchiectasis who were treated in Cangzhou Central Hospital from January 2017 to December 2018.Data were collected，including clinical characteristics（gender，age，BMI，smoking history，course of bronchiectasis，number of exacerbations per year，sputum volume，history of hemoptysis，cause of bronchiectasis，colonization of Pseudomonas aeruginosa），results of high-resolution CT（HRCT）of the chest，lung function test parameters（FEV1%pred，FVC%pred，FEV1/FVC ratio，increase in FEV1 after using the bronchodilator），induced sputum test parameters（IL-8，IL-6 and IL-13）and sputum cell classification，and FeNO.Pearson correlation analysis was used to explore the associations of some induced sputum test parameters with FeNO and lung function test parameters.Results　Patients with bronchiectasis can be divided into neutrophilic type （32 cases），eosinophilic type （10 cases）， mixed granulocytic type （6 cases）and paucigranulocytic type（14 cases）according to the cytological classification of induced sputum.The levels of IL-8 and IL-6 in neutrophilic type were higher compared with those of eosinophilic and paucigranulocytic types，while the level of IL-13，FeNO，increase in FEV1 after using the bronchodilator were lower than those of eosinophilic and mixed granulocytic types（P<0.05）.The neutrophilic type had more severe bronchiectasis in HRCT（P<0.05）.The eosinophilic type had lower levels of IL-8 and IL-6 than mixed granulocytic type，greater level of IL-13 and FeNO than paucigranulocytic type，and more increase of FEV1 after using the bronchodilator than mixed granulocytic and paucigranulocytic types（P<0.05）.The increase in FEV1 after using the bronchodilator，levels of IL-8，IL-6，IL-13，and FeNO of mixed granulocytic type were higher than those of paucigranulocytic type（P<0.05）.The level of sputum IL-8 was positively correlated with the score of HRCT（r=0.625）and the percentage of neutrophils（r=0.711），and was negatively correlated with FEV1%pred（r=-0.327），FVC%pred（r=-0.401），FEV1/FVC ratio（r=-0.398），increase in FEV1 after using the bronchodilator（r=-0.312，P<0.05）.IL-6 was positively correlated with the score of HRCT（r=0.342）and the percentage of neutrophils（r=0.221，P<0.05）.The level of IL-13 was correlated with the increase in FEV1 after using the bronchodilator（r=0.439），the percentage of eosinophils（r=0.536），and FeNO（r=0.526，P<0.05）.The percentage of neutrophils was positively correlated with the score of HRCT（r=0.548），and negatively correlated with FEV1%pred（r=-0.372），FVC%pred（r=-0.345），FEV1/FVC ratio（r=-0.253），increase in FEV1 after using the bronchodilator（r=-0.346），the percentage of eosinophils（r=-0.553，P<0.05）.The percentage of eosinophils was positively correlated with the increase in FEV1 after using the bronchodilator（r=0.522）and FeNO（r=0.576，P<0.05）.FeNO was correlated with the increase in FEV1 after using the bronchodilator（r=0.423，P<0.05）.Conclusion　The induced sputum cell classification，IL-8，IL-6，IL-13 levels and FeNO were related with the clinical indicators of patients with bronchiectasis，which may be helpful for the comprehensive evaluation of bronchiectasis.

Key words: Bronchiectasis, Induced sputum, FeNO, Lung function tests, Inflammatory cytokine

摘要： 背景　支气管扩张症（简称支扩症）是常见的气道慢性炎症性疾病，但患者存在明显异质性。诱导痰及呼出气一氧化氮（FeNO）检查已广泛应用于哮喘及慢性阻塞性肺疾病的病情评估，但是否有助于评估支扩症患者的气道炎症状态尚缺乏相关临床研究。目的　评估诱导痰及FeNO检查与支扩症患者临床特征、肺功能指标的关系，探讨无创气道炎症检查在支扩症患者中的应用价值。方法　选择2017年1月—2018年12月于沧州市中心医院就诊的稳定期支扩症患者62例为研究对象，记录患者性别、年龄、体质指数（BMI）、吸烟史、病程、急性加重次数、痰量、咯血史、发生支扩症的病因、铜绿假单胞菌定植等情况，并进行胸部高分辨率CT（HRCT）检查，记录HRCT评分；进行肺功能检查，记录第1秒用力呼气末容积占预计值的百分比（FEV1%pred）、用力肺活量占预计值的百分比（FVC%pred）、第1秒用力呼气末容积占用力肺活量的百分比（FEV1/FVC）、应用支气管扩张剂后第1秒用力呼气末容积（FEV1）增加量；进行诱导痰检查，测定白介素（IL）-8、IL-6、IL-13水平，观察细胞分型情况；进行FeNO检查，并记录FeNO。采用Pearson相关性分析探讨诱导痰检查的部分指标与FeNO及肺检查指标的相关性。结果　支扩症患者按照诱导痰细胞学分类可以分为中性粒细胞型（32例）、嗜酸粒细胞型（10例）、混合细胞型（6例）、寡细胞型（14例）。中性粒细胞型患者IL-8、IL-6水平高于嗜酸粒细胞型、寡细胞型患者，IL-13水平、FeNO、应用支气管扩张剂后FEV1增加量低于嗜酸粒细胞型、混合细胞型患者，HRCT评分高于嗜酸粒细胞型、混合细胞型、寡细胞型患者（P<0.05）；嗜酸粒细胞型患者IL-8、IL-6水平低于混合细胞型患者，IL-13水平、FeNO高于寡细胞型患者，应用支气管扩张剂后FEV1增加量高于混合细胞型、寡细胞型患者（P<0.05）；混合细胞型患者应用支气管扩张剂后FEV1增加量、IL-8水平、IL-6水平、IL-13水平、FeNO高于寡细胞型患者（P<0.05）。IL-8水平与HRCT评分（r=0.625）、中性粒细胞百分比（r=0.711）呈正相关，与FEV1%pred（r=-0.327）、FVC%pred（r=-0.401）、FEV1/FVC（r=-0.398）、应用支气管扩张剂后FEV1增加量（r=-0.312）呈负相关（P<0.05）；IL-6水平与HRCT评分（r=0.342）、中性粒细胞百分比（r=0.221）呈正相关（P<0.05）；IL-13水平与应用支气管扩张剂后FEV1增加量（r=0.439）、嗜酸粒细胞百分比（r=0.536）、FeNO（r=0.526）呈正相关（P<0.05）；中性粒细胞百分比与HRCT评分（r=0.548）呈正相关，与FEV1%pred（r=-0.372）、FVC%pred（r=-0.345）、FEV1/FVC（r=-0.253）、应用支气管扩张剂后FEV1增加量（r=-0.346）、嗜酸粒细胞百分比（r=-0.553）呈负相关（P<0.05）；嗜酸粒细胞百分比与应用支气管扩张剂后FEV1增加量（r=0.522）、FeNO（r=0.576）呈正相关（P<0.05）；FeNO与应用支气管扩张剂后FEV1增加量（r=0.423）呈正相关（P<0.05）。结论　诱导痰细胞分类、IL-8、IL-6、IL-13水平及FeNO与支扩症患者临床指标相关，有助于支扩症患者病情的综合评价。

关键词: 支气管扩张症, 诱导痰, 呼出气一氧化氮, 肺功能, 炎性因子

WANG Xiaosheng,KANG Xiaoling,ZHANG Ying, et al. Role of Induced Sputum and Fractional Exhaled Nitric Oxide Test for Assessing Inflammation in Patients with Bronchiectasis　[J]. Chinese General Practice, 2021, 24(5): 546-550. DOI: 10.12114/j.issn.1007-9572.2020.00.587.
王晓晟,康筱玲,张颖等. 诱导痰及呼出气一氧化氮检查在支气管扩张症患者中的应用价值[J]. 中国全科医学, 2021, 24(5): 546-550. DOI: 10.12114/j.issn.1007-9572.2020.00.587.

References

［1］成人支气管扩张症诊治专家共识编写组.成人支气管扩张症诊治专家共识［J］．中华结核和呼吸杂志，2012，35（7）：485-492．DOI：10.3760/cma.j.issn.1001-0939.2012.07.003.
［2］陈荣昌，关伟杰，钟南山.支气管扩张症：需要更多的关注和研究［J］．中华结核和呼吸杂志，2017，40（1）：5-7．
［3］ALIBERTI S，LONNI S，DORE S，et al．Clinical phenotypes in adult patients with bronchiectasis［J］．Eur Respir J，2016，47（4）：1113-1122．DOI：10.1183/13993003.01899-2015.
［4］GARTH J，BARNES J W，KRICK S.Targeting cytokines as evolving treatment strategies in chronic inflammatory airway diseases［J］．Int J Mol Sci，2018，19（11）：E3402．
［5］WEI P，YANG J W，LU H W，et al．Combined inhaled corticosteroid and long-acting β2-adrenergic agonist therapy for noncystic fibrosis bronchiectasis with airflow limitation：an observational study［J］．Medicine（Baltimore），2016，95（42）：e5116．DOI：10.1097/MD.0000000000005116.
［6］SMITH I E，JURRIAANS E，DIEDERICH S，et al．Chronic sputum production：correlations between clinical features and findings on high resolution computed tomographic scanning of the chest［J］．Thorax，1996，51（9）：914-918.
［7］COWAN D C，COWAN J O，PALMAY R，et al．Effects of steroid therapy on inflammatory cell subtypes in asthma［J］．Thorax，2010，65（5）：384-390．DOI：10.1136/thx.2009.126722.
［8］American Thoracic Society，European Respiratory Society.ATS/ERS recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide，2005［J］．Am J Respir Crit Care Med，2005，171（8）：912-930．DOI：10.1164/rccm.200406-710ST.
［9］REYNOLDS C J，QUIGLEY K，CHENG X M，et al．Lung defense through IL-8 carries a cost of chronic lung remodeling and impaired function［J］．Am J Respir Cell Mol Biol，2018，59（5）：557-571．DOI：10.1165/rcmb.2018-0007OC.
［10］WOLTMANN G，MCNULTY C A，DEWSON G，et al．Interleukin-13 induces PSGL-1/P-selectin-dependent adhesion of eosinophils，but not neutrophils，to human umbilical vein endothelial cells under flow［J］．Blood，2000，95（10）：3146-3152.
［11］NTONTSI P，PAPATHANASSIOU E，LOUKIDES S，et al．Targeted anti-IL-13 therapies in asthma：current data and future perspectives［J］．Expert Opin Investig Drugs，2018，27（2）：179-186．DOI：10.1080/13543784.2018.1427729.
［12］SCHMIDT H，BRAUBACH P，SCHILPP C，et al．IL-13 impairs tight junctions in airway epithelia［J］．Int J Mol Sci，2019，20（13）：E3222．DOI：10.3390/ijms20133222.
［13］CHO Y J，LIM H J，PARK J S，et al．Measurement of fractional exhaled nitric oxide in stable bronchiectasis［J］．Tuberc Respir Dis（Seoul），2013，74（1）：7-14．
［14］TELENGA E D，KERSTJENS H A，TEN HACKEN N H，et al．Inflammation and corticosteroid responsiveness in ex-，current- and never-smoking asthmatics［J］．BMC Pulm Med，2013，13：58．DOI：10.1186/1471-2466-13-58.

[1]	CHEN Ai, SUN Lina, REN Jiaqi, CHANG Chun, CHEN Yahong, SUN Yongchang. Prevalence and Clinical Characteristics of Allergic Bronchopulmonary Aspergillosis in Patients with Bronchiectasis [J]. Chinese General Practice, 2023, 26(30): 3797-3800.
[2]	Jiarui GUAN, Jiaming REN, Yang XIE, Peng ZHANG. Application of Minimal Clinically Important Difference in Outcome Assessment Tools for Bronchiectasis Treatment [J]. Chinese General Practice, 2022, 25(30): 3739-3746,3754.
[3]	CHEN An, CAO Xiao, ZHANG Huilin, LIAN Jianfeng. Effect of Acupuncture as an Adjuvant Therapy for Intravenous Thrombolytic Treatment on Peripheral Inflammatory Factors and Neurologic Function in Patients with Acute Ischemic Stroke [J]. Chinese General Practice, 2022, 25(03): 331-335.
[4]	LYU Yanhang，WU Shanshan，WANG Zhenchang，YE Xuejin，FU Yanqing，DUAN Guijiao，SU Xiaowen，NONG Xiaoxin. Clinical，Serum Inflammatory Cytokine，Immune，and Oxidative Stress Responses to Rougan Huaxian Granules with Transplantation of Bone Mesenchymal Stem Cells in Decompensated Cirrhosis Patients　 [J]. Chinese General Practice, 2021, 24(3): 355-362.
[5]	LIU Xianbing，LI Fang，XU Ning，ZHU Lifen，ZHENG Xiaoyan. The Effects of Smoking Cessation Intervention on Local Airway Immunity and Life Quality in Patients with Chronic Obstructive Pulmonary Disease in Early Stable Stage　 [J]. Chinese General Practice, 2021, 24(23): 2927-2939.
[6]	WANG Jiayan，XU Yujiao，LIN Xiaowei，CHEN Qi，ZHANG Guanzhuang，HUANG Hongmin. Effect of Soaking and Fumigation Washing Therapy of Modified Guizhi Decoction on Patients with Hemiplegia in Acute Stage of Ischemic Stroke（Meridian Obstruction）　 [J]. Chinese General Practice, 2020, 23(30): 3851-3855.
[7]	XU Lin，LU Ping，YAO Hongmei，ZHANG Yiling*. Association of Expression of Human Group X Secreted Phospholipase A2 with Inflammatory Indicators in the Serum in Patients with Bronchiectasis and Infection [J]. Chinese General Practice, 2020, 23(24): 3034-3039.